Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM)and Adult Polmyositis (PM) - Rituximab in myositis (RIM)

Phase 1

• Conditions: Adult polymyositis or adult dermatomyositis or juvenile dermatomyositis.; MedDRA version: 9.1Level: LLTClassification code 10036102Term: Polymyositis

• Registration Number: EUCTR2006-000078-65-CZ
• Lead Sponsor: Karolinska University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-18
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 202

Inclusion Criteria

1. Adults with definite or probable DM or PM and pediatric patients five years of age and over with definite or probable JDM by the criteria of Bohan and Peter. Patients without the rash of DM will require a muscle biopsy (not necessarily done at the enrollement) compatible with PM as determined by an experienced pathologist. In order to be enrolled with a diagnosis of refractory PM, patients' medical information will be reviewed and the diagnosis confirmed by a 3-member Adjudication Committee consisiting of 3 Steering Committee members/investigators. This adjudication process is necessary to exclude mimics of polyomyositis including but not limited to inclusion body myositis, toxic or metabolic myopathies and adult onset muscular dystrophies.
2. A diagnosis of JDM based on an age of onset (i.e. first symptom of myositis or the rash of dermatomyositis)< 18 years of age.
3. Disease duration > 6 months from diagnosis of myositis.
4. Refractory myositis as defined by the intolerance to or an inadequate response to corticosteroids plus an adequate regimen of at least one other IS agent such as azathioprine, methotrexate, IVIg, mycophenolate mofetil, cyclophosphamide, tacrolimus or cyclosporine A. The definition of intolerance is: side effects that require discontinuation of the medication or an underlying condition that precludes the further use of the medication. An adequate corticosteroid treatment trial is as follows:
- Adult IIM: prednisone (or an equivalent corticosteroid) at a dose of at least 60mg/day for one month
- JDM: 1.0mg/kg/day prednisone for at least one month
5. Baseline manual muscle testing which is based on a maximum MMT-8 score of 150. Subjects must have a score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures include the following:
- Patient/Parent global VAS with a minimum value of 2.0 cm on a 10 cm scale
- MD Global VAS with a minimum value of 2.0 cm on a 10 cm scale
- CHAQ/HAQ disability index witha minimum value of 0.25
- Elevation of at least one of the muscle enzymes (which includes creatinine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (AST) at a minimum level of 1.3x ULN
If more than one muscle enzyme is identified as being elevated and meeting the above guidelines then the most abnormal will be selected and this enzyme will be the target enzyme followed to evaluate disease improvement or worsening.
- Global extramuscular disease activity score with a minimum value of 1.0cm on a 10cm VAS scale (this measure is the physician´s composite evaluation and is based on assessments of activity scores on the constitutional, cutaneous, sceletal, gastrointestinal, pulmonary and cardiac scales of the Myositis Disease Activity Assessment Tool (MDAAT)
6. If on Prednisone, the dose must be stable for 4 weeks prior to the screening visit (recommend < 1.0mg/kg(day)
7. Background therapy with at least 1 non-corticosteroid immunosupressive agent is required at a stable dose for at least 6 weeks prior to the screening visit.
- The IS agents include: methotrexate, azathioprine, cyclosporine, tacrolimus, cyclophosphamiode or mycophenolate mofetil
8. If an IS agennt was discontinued prior to the screening visit then there must be a:
-4week washout for methotrexate
-8 week washout for any other IS agent
9. If on plaquenil the dose should be stable for 8 weeks prior to Visit 1
10. If on statin agents the dose should be stable for 8 weeks prior to Visit 1
11. Ability

Exclusion Criteria

1. Drug induced myositis (myositis in patients taking medication known to induce myositis-like syndromes, including but not limited to statin agents, fibric acid derivates, colchicine, and hydroxychloroquine).
2. Use of colchicine during study participation is not allowed.
3. Juvenile polymyositis; inclusion body myositis; cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer except basal or squamous cell skin cancer or carcinoma in situ of the cervix if at least 5 years since excision.
4. Myositis in overlap with another connective tissue disease (CTD) that precludes the accurate assessment of a treatment response (the 3-member committee discussed inder Inclusion Criteria 1 above will also determine the eligibility of such patients with myositis and an associated CTD).
5. History of receiving live vaccination 4 weeks prior to initiation of study treatment.
6. Joint disease or other musculoskeletal condition, which precludes the ability to quantitative muscle strength
7. Known hypersensitivity to murine proteins
8. Concomitant illness that would prevent adequate patient assessment or pose an added risk for study paticipants:
-reccurent or chronic infections, including HIV, hepatitis B and C
-known liver disease (i.e. cirrhosis or other conditions compromising the synthetic function of the liver)
-disorders that would preclude accurate assessment of neuromuscular function
-cardiomyopathy/congestive heart failure/arrythmia (or NYHA Clasification III or IV disease)
-psychiatric illness that precludes compliance or neuromuscular assessment
-serum creatinine > 2.0mg/dl
-IgG or IgM levels at baseline that are below the normal range (for pediatrics age adjusted normal ranges will be followed)
9. Pregnant females or nursing mothers
10. Life threatening non-myositis illness that would interfere with patient´s ability to complete the study.
11. Known or suspected history of drug or alcohol abuse within the past 6 months as determined by the medical record or patient interview.
12. Anticipated poor compliance
13. Participation in another clinical (experimental) study within 30 days of screening visit.
14. Any history or evidence of severe illness or any other condition that would make the patient, in the opinion of the investigator unsuitable for the study.
15. Any history of receiving rituximab.
16. Evidence of prior infection of Hepatitis B and Hepatitis C
17. Initiation of an excercise program within 4 weeks of screening visit or initiation of an excercise program during the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of intravenous rituximab in a randomized, double-blind, placebo-controlled, multicenter phase II/III trial of refractory myositis in adults and children.;Secondary Objective: To assess the determinants of treatment response and disease pathogenesis in patients receiving rituximab.;Primary end point(s): The primary endpoint of this trial is to compare the time to achieve the definition of improvement (DOI) between the two groups of rituximab-treated patients.